Time Magazine Questions Statin Risks and Benefits in Women, But Experts Say Drugs Safe and Effective

From Heartwire
Michael O'Riordan

March 30, 2010 (New York, New York) — Do statins work equally for men and women? That's the question put forth by Time magazine last week in an article examining the relative risks and benefits between the sexes. While some question whether the evidence is strong enough to support their use, most experts believe that the lipid-lowering medications have undeniable value in women and worry the Time article may cause undue fear or drug cessations.

"I think a take-home point is that, on average, women have lower risks of coronary heart disease than men, at any age and over a lifetime," Dr James Stein (University of Wisconsin, Madison) told heartwire . "So it is more difficult for a woman to reach risk thresholds that indicate need for treatment. But heart disease is the leading killer of women. If you are at increased risk, it does not matter if you are male or female--you need intervention, and statins are effective and safe in both men and women."

The article, by Catherine Elton, documents the case of one woman, "healthy by nearly every measure--except her cholesterol level," treated with a statin that led to severe muscle pain. Eventually, the myopathy is so severe, she stops the statin. Another woman, with high cholesterol and diabetes, begins treatment with a statin and soon forgets how to do basic math and gets lost driving to familiar places.

"Researchers also don't know why women are more likely than men to suffer side effects from statins and many other drugs but posit that lower body weight and hormonal fluctuations play a role," writes Elton. "Biological explanations aside, the larger point is the same: with any treatment, the benefits should outweigh the risks."

Dr Richard Karas (Tufts University Medical Center, Boston, MA) told heartwire the article is "having a large impact in the community" and that he disagrees with the fear and uncertainty it may have caused. Patients are upset, he added, and are calling clinicians asking if they should stop their medication.

Lower Absolute Risk in Women

Speaking with heartwire, Dr James de Lemos (University of Texas Southwestern, Dallas) said that he "finds it hard to believe there are any biological differences in the effects of statins between the sexes." The relevant issue, he said, is that women have a lower absolute risk of ischemic events than men, and this alters the risk/benefit profile, as well as the relative costs. He added that "myopathy is a bit more common in women, but usually in older women, usually treated with higher doses of statins." He said statin therapy typically doesn't pose a problem in younger women treated with the drugs.

Regarding the side effects, Karas noted that women are smaller and tend to be older when they are prescribed statins, and this might contribute to the different side-effect profile between the sexes. Still, these differences are not reasons enough to think the drugs would benefit women to a lesser extent than men, especially since LDL cholesterol predicts coronary heart disease risk in women.

Dr Scott Grundy (University of Texas Southwestern, Dallas) told Time that the "underrepresentation of women in drug trials does not discount statins' benefit; it results only in a failure to show a statistically significant effect," something most experts polled by heartwire also believe.

Grundy highlighted a recent analysis of Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER), a study he believes provides evidence supporting the use of the cholesterol-lowering medication in women. In that analysis, looking just at women enrolled in JUPITER, led by Dr Samia Mora (Brigham and Women's Hospital, Boston, MA), rosuvastatin 20 mg significantly reduced the relative risk of the primary end point--a composite of MI, stroke, revascularization, hospitalization for unstable angina, and death from cardiovascular causes--by 46% [2]. The reduction in risk was supported by evidence in a meta-analysis of 13 154 women included in primary-prevention statin trials.

In addition to these findings, Stein pointed to the Cholesterol Treatment Trialists' collaboration, a prospective meta-analysis of data from 90 056 subjects in 14 randomized statin trials from 1994 to 2000, a study that found no difference in statin effectiveness by sex.

In Time, Elton writes that the women were more likely to develop diabetes than men in JUPITER and that the number needed to treat to prevent one event was also higher. Moreover, the article suggested that the reduction in clinical events was the result of larger reductions in softer end points, such as hospitalization for unstable angina and revascularization.

Dr Rita Redberg (University of California San Francisco), who is quoted in the Time article, told heartwire the key issue is that "millions of healthy American women are taking statins, which have never been shown to reduce MI or lengthen life and have an untold number of side effects, worse in women than men."

To heartwire , de Lemos said these findings are likely the result of a lack of statistical power. With fewer women and their lower baseline risk, it is harder to demonstrate a benefit, he said. Dr Pamela Douglas (Duke University, Durham, NC) agreed, adding that this "also may mean that the threshold for use should be different in men and women, but it doesn't mean statins don't have value in women. de Lemos added that clinicians are now beginning to address the importance of lifetime risk, and from this perspective, even in women with lower baseline risk, statin therapy reduces clinical events.

In response to the Time article, as well as a recent Food and Drug Administration advisory released last week about simvastatin (Zocor, Merck/Schering-Plough), the American Heart Association (AHA) issued a commentary reminding "patients that controlling cholesterol is critical for preventing coronary heart disease and reducing heart attack." It says that myopathy is uncommon and reversible, but it can be a reason to discontinue or reduce the dose of treatment.

"Because of the well-documented benefit of cholesterol lowering with statins, the association advises that patients respect the benefit of statin therapy and consider discontinuation only after a discussion with the appropriate healthcare provider," according to the AHA. "For the person who experiences myopathy with a statin, other alternatives should be discussed with their physician. Patients who are taking statins and not experiencing any side effects should continue to take their medication unless advised for other reasons to stop by their healthcare provider."

Karas reports receiving research grants from AstraZeneca and Kos Pharmaceuticals; serving on the speakers' bureaus of and/or receiving honoraria from Kos, AstraZeneca, Merck, and Pfizer; and serving as a consultant to Kos Pharmaceuticals. de Lemos reports consulting fees/honoraria from Tethys and Johnson & Johnson; speaker's bureau fees from the Bristol-Myers Squibb/Sanofi-Aventis partnership; research grants from Roche; serving on the data safety and monitoring board of Bristol-Myers Squibb; and financial benefits from AstraZeneca and Daiichi-Sankyo. Stein reports research grants from Siemens and serving on the data safety and monitoring board of Abbott, Lilly, and Takeda. Grundy reports grant and research support from Bristol-Myers Squibb, Merck, and Pfizer and serving as a consultant or on the advisory board of Merck, Merck/Schering-Plough, AstraZeneca, Pfizer, and GlaxoSmithKline. Redberg reports no conflicts of interest.

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